We used immunoperoxidase methods employing antibodies against involucrin and filaggrin, both markers of squamous terminal differentiation, to study squamous metaplastic transformation in the human endocervix. Expression of involucrin and filaggrin was restricted to squamous metaplastic cells whereas columnar epithelial cells were constantly negative. Immature squamous metaplastic epithelium also showed a positive immunostaining. In mature squamous metaplasia a suprabasal homogeneous staining pattern similar to that found in the exocervical epithelium was detected, although with full-thickness filaggrin immunoreactivity in 45% of cases (P<0.05). These results support the hypothesis of an epithelial origin of reserve subcolumnar cells, and suggest that precocious squamous differentiation seems to take place in metaplastic cells of the human endocervix.